www.nature.
com/scientificreports
OPEN
received: 17 November 2015
accepted: 05 February 2016
Published: 25 February 2016
Scientific Reports | 6:22089 | DOI: 10.1038/srep22089
Prognostic significance of
neutrophil-to-lymphocyte ratio
in prostate cancer: evidence from
16,266 patients
Xiaobin Gu, Xianshu Gao, Xiaoying Li, Xin Qi, Mingwei Ma, Shangbin Qin, Hao Yu,
Shaoqian Sun, Dong Zhou & Wen Wang
This study was aimed to investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in
patients with prostate cancer (PCa). A meta-analysis including 14 publications (15 cohorts) with 16,266
patients was performed to evaluate the association between NLR and overall survival (OS), progression-
free survival (PFS)/recurrence-free survival (RFS) in PCa using hazard ratio (HR) and 95% confidence
intervals (95% CI). The combining data showed that increased NLR predict poor OS (HR = 1.38,
95%CI: 1.22–1.56) and PFS/RFS (HR = 1.24, 95%CI 1.05–1.46) in PCa. Stratified analysis by PCa type,
sample size, ethnicity and NLR cut-off value revealed that NLR showed consistent prognostic value in
metastatic castration-resistant prostate cancer (mCRPC) patients and predict poor PFS/RFS in Asians,
but not in Caucasians. These statistical data suggested that increased NLR could predict poor prognosis
in patients with PCa.
Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer-related
death among men in the western world, accounting for 220,800 new cases and 27,540 deaths in the US annu-
ally1. The incidence of prostate cancer varies remarkably in different countries and regions, which increased
significantly during the past few decades due to diverse approaches diagnosing PCa. Despite different treatment
methods including radical prostatectomy, hormone deprivation therapy, radiation therapy and chemotherapy
were applied, most tumors relapse in 2 years to the castration-resistant state and the prognosis of PCa remains
disappointing2. Given this, it is of interest for clinicians to stratify the high risk PCa patients who are prone to
tumor recurrence and poor prognosis so that clinicians could further identify optimal treatment strategies3.
Accumulating evidence has shown that inflammation response is closely associated with tumorigenesis and
tumor progression4,5. The interactions between tumor and inflammation were complex and involved different
mechanisms. Inflammation plays an important role in every single step in carcinogenesis, involving tumor ini-
tiation, angiogenesis promotion, apoptosis inhibition and tumor metastasis6. The changes in systemic inflam-
matory response can be reflected by measurement of various blood-based parameters. A variety of blood-based
indexes including C-reactive protein (CRP), modified Glasgow Prognostic Score (mGPS), platelets count and
neutrophil-to-lymphocyte ratio (NLR) have been extensively explored to predict prognosis of cancer patients7–9.
A large amount of studies have reported that elevation of NLR was associated with poor clinical outcomes in var-
ious malignant tumors10,11. In recent years, several studies have reported that an elevation in NLR correlated with
biological tumor recurrence and poor prognosis in patients with PCa12–14. However, some other studies did not
detect the prognostic significance of NLR in PCa patients15,16. Therefore, it is necessary to systematically clarify
the prognostic significance of NLR in PCa by the approach of meta-analysis.
The current study was designed to evaluate the prognostic value of elevated NLR for overall survival (OS)
and progress-free survival (PFS)/recurrence-free survival (RFS) in patients with PCa by pooling results from
published data.
Department of Radiation Oncology, Peking University First Hospital, Beijing 100034, China. Correspondence and
requests for materials should be addressed to X.G. (email: doctorgaoxs@126.com)
1
www.nature.com/scientificreports/

Figure 1.  The flow chart of literature selection.

Cut-off
Sample value Of Survival
Study Year Country Ethnicity size PCa type Treatment method NLR analysis
Shafique16 2012 UK Caucasian 709 All PCa NR 5 OS
Linton15 2013 Australia Caucasian 182 mCRPC Chemotherapy 5 OS
Nuhn12 2014 USA Caucasian 247 mCRPC Chemotherapy 3 OS
Sumbul25 2014 Turkey Asian 33 mCRPC Chemotherapy 3 PFS
Templeton13 2014 Canada Caucasian 357 mCRPC Chemotherapy 3 OS
Bahig24 2015 Canada Caucasian 950 Localized PCa Radiotherapy 3 OS,PFS
Kwon23 2015 USA Caucasian 217 Localized PCa Prostatectomy 2.6 RFS
Langsenlehner14 2015 Austria Caucasian 415 Localized PCa Radiotherapy 5 OS,PFS
Lee22 2015 Korea Asian 1367 Localized PCa Prostatectomy 2.5 RFS
Lorente21 2015 UK Caucasian 755 mCRPC Chemotherapy 3 OS,PFS
Poyet20 2015 Switzerland Caucasian 399 Localized PCa Prostatectomy 2.67 RFS
Sharma19 2015 USA Caucasian 8350 Localized PCa Prostatectomy 5 OS,PFS
Soest117 2015 Netherland Caucasian 1224 mCRPC Chemotherapy 2 OS
Soest217 2015 Netherland Caucasian 1006 mCRPC Chemotherapy 2.1 OS
Yao18 2015 Japan Asian 55 mCRPC Chemotherapy 3.5 OS,PFS

Table 1.  Characteristics of the included studies. NR: not reported; OS: overall survival; PFS: progression-free
survival.

Results
Selection and characteristics of included eligible studies.  The selection process was shown in Fig. 1.
Through initial searching of the database, 197 records were retrieved and screened by title and abstract. 174
records were discarded after title and abstracts screening because they were duplicate records, reviews, irrel-
evant studies and nonhuman studies. 23 full-text records were further evaluated for eligibility. Of them, nine
studies were eliminated due to following reasons: five did not provide the survival information, three provided
insufficient data to calculate HR and 95%CI, one was a comment. Soest et al.17 included two independent rand-
omized phase III trials in their paper, we marked the cohorts as Soest1 and Soest2. Finally, 14 publications12–25
(15 cohorts) with 16,266 patients published between 2012 and 2015 were included in the meta-analysis process.
The basic information of the included studies was summarized in Table 1. 11 studies (12 cohorts)12–17,19–21,23,24
were from western countries, 3 studies18,22,25 were from Asian countries. Of the 14 studies (15 cohorts), 10 studies
(11 cohorts)12–19,21,24 investigated the prognostic role of NLR on OS, 9 studies14,18–25 investigated prognostic role
of NLR on PFS/RFS.

Scientific Reports | 6:22089 | DOI: 10.1038/srep22089 2

www.nature.com/scientificreports/

Figure 2.  Meta-analysis of the association between elevated NLR and OS.

NLR and OS in PCa.  11 cohorts with 14,250 patients provided the data of NLR and OS in PCa. The pooled
HR of 1.38 (95%CI: 1.22–1.56) with heterogeneity (Ph =  0.002, I2 =  64.1%) showed elevated NLR predicted
shorter OS in patients with PCa (Fig. 2, Table 2).

NLR and PFS/RFS in PCa.  9 cohorts with 12541 patients presented the data of pretreatment NLR and PFS/
RFS in PCa. Though with heterogeneity (Ph =  0.003, I2 =  65.3%), a significant correlation between increased NLR
and poor PFS/RFS (HR =  1.24, 95%CI: 1.05–1.46) was detected according to our pooled data (Fig. 3, Table 2).
Interestingly, increased NLR predicted shorter RFS/PFS in Asian populations (HR =  1.42, 95%CI: 1.11–1.82), but
not in Caucasian populations (HR =  1.18, 95%CI: 0.98–1.43).

Subgroup analysis and meta-regression.  Subgroup analysis and meta-regression were carried out
to investigate the sources of heterogeneity. With respect to the correlation between NLR and OS, subgroup
analysis stratified by PCa types showed that the combined HRs were 1.44 (95%CI: 1.32–1.57) for metastatic
castration-resistant prostate cancer (mCRPC) and 1.16 (95%CI: 0.98–1.36) for localized PCa. Subgroup analysis
dichotomized by sample size(> 400 vs. < 400) and NLR cut-off value (≤ 3 vs. > 3) did not change the results sub-
stantially(Table 2). Meta-regression showed PCa types could be the potential source of heterogeneity (p =  0.01).
With regard to the correlation between NLR and PFS/RFS, subgroup analysis showed similar results with total
results. Notably, the pooled HR for Asian ethnicity was 1.42 (95%CI: 1.11–1.82) without significant heterogeneity
(Ph =  0.345, I2 =  6%). In addition, the pooled HR for mCRPC was 1.45 (95%CI: 1.19–1.77) with good homoge-
neity (Ph =  0.37, I2 =  0) (Table 2).

Sensitivity analysis.  Omitting any single study by turn, sensitivity analysis demonstrated that the combined
HRs for OS and PFS/RFS did not significantly alter (Fig. 4).

Publication bias.  Evaluation of publication bias using Begg’s test (p <  0.05 was considered as statistical sig-
nificant) demonstrated that there was no significant publication bias in OS and PFS/RFS studies (p =  0.119 and
p =  0.251, respectively)(Fig. 5).

Discussion
In the present study, we aimed to explore the prognostic value of NLR in patients with PCa. A total of 14 studies
(15 cohorts) containing 16,266 patients were included in this meta-analysis to calculate pooled HR. The results
showed that increased pretreatment NLR was associated with poor OS(HR =  1.38, 95%CI: 1.22–1.56) and PFS/
RFS (HR =  1.24, 95%CI: 1.05–1.46), though with heterogeneity. Subgroup analysis divided by ethnicity, PCa
type, sample sizes and NLR cut-off value did not significantly change the main results. Of note, subgroup anal-
ysis demonstrated that pretreatment NLR had enhanced prognostic efficiency for OS and PFS/RFS in mCRPC
(HR =  1.44, 95%CI: 1.32–1.57 for OS and HR =  1.45,95%CI: 1.19–1.77 for RFS/PFS) without significant het-
erogeneity. In addition, elevated NLR also predicted poor PFS/RFS in Asian populations, but not in Caucasian
population. To our knowledge, our study is the first meta-analysis exploring the prognostic effects of increased
NLR in OS and PFS/RFS in patients with PCa.

Scientific Reports | 6:22089 | DOI: 10.1038/srep22089 3

www.nature.com/scientificreports/

Figure 3.  Meta-analysis of the association between elevated NLR and PFS/RFS.

Heterogeneity
No. of No. of Meta-regression
Outcome Variable studies patients Model HR (95%CI) Ph I2 (%) P value
OS All 11 14250 R 1.38(1.22–1.56) 0.002 64.1
PCa type 0.01
mCRPC 7 3826 F 1.44(1.32–1.57) 0.238 25
Localized PCa 3 9715 R 1.16(0.98–1.36) 0.109 54.9
All PCa 1 709 — 1.55(0.97–2.47) — —
Sample size 0.19
> 400 7 13409 R 1.32(1.16–1.49) 0.005 67.8
< 400 4 841 F 1.61(1.31–1.99) 0.252 26.6
NLR cut-off 0.756
≤ 3 6 4539 R 1.34(1.24–1.45) 0.009 67.3
> 3 5 9711 R 1.18(1.06–1.31) 0.066 54.6
PFS/RFS All 9 12541 R 1.24(1.05–1.46) 0.003 65.3
Ethnicity
Asian 3 1455 F 1.42(1.11–1.82) 0.345 6
Caucasian 6 11086 R 1.18(0.98–1.43) 0.003 72.3
PCa type
mCRPC 3 843 F 1.45(1.19–1.77) 0.37 0
Localized PCa 6 11698 R 1.16(0.97–1.39) 0.01 66.6
Sample size
> 400 5 11837 R 1.28(1.00–1.65) 0.001 78.8
< 400 4 704 F 1.14(0.98–1.33) 0.255 26.1
NLR cut-off
≤ 3 6 3721 F 1.17(1.06–1.29) 0.203 30.9
> 3 3 8820 R 1.82(0.77–4.3) 0 87.3

Table 2.  Summary of the subgroup analysis results of NLR on OS and PFS/RFS. F: fixed-effects model; R:
random-effects model.

Growing evidence has indicated that inflammatory response could be heavily involved in the occurrence and
development of different cancer types26–28. Studies revealed that inflammation-related neutrophils and immuno-
cytes including lymphocytes were indispensable participants in tumorigenesis29. Inflammation exerts an impor-
tant role in tumor formation and development through facilitating angiogenesis, proliferation and protecting
tumors from apoptosis. By secreting a variety of chemokines, tumor cells could attract pro-inflammatory cells

Scientific Reports | 6:22089 | DOI: 10.1038/srep22089 4

www.nature.com/scientificreports/

Figure 4.  Sensitivity analysis on the relationship between NLR and (A) OS and (B) PFS/RFS in PCa.

Figure 5.  Begg’s funnel plot of publication bias test for (A) OS and (B) PFS/RFS in PCa.

into tumor microenvironment, subsequently, an array of cytokines produced by neutrophils stimulate tumor
cells growth30. Of these inflammatory parameters reflecting the systemic inflammatory response, an increased
neutrophil-to-lymphocyte ratio (NLR) has been found valuable to predict clinical outcome of cancer patients31.
Additionally, NLR is obtained from routine blood test, making it an easily available and reliable marker. A large
amount of studies have showed the correlation between increased pretreatment NLR and poor prognosis in dif-
ferent malignant tumors including gastric cancer, colorectal cancer, breast cancer, prostate cancer, soft-tissue
sarcoma and non-small cell lung cancer17,27,32–35.
Our results demonstrated that elevated NLR was in associated poor OS and PFS/RFS in patients with PCa,
which was in accordance with the results from meta-analysis with other cancer types34,36,37. We have noted that
a recently published work investigated the prognostic value of NLR in various solid tumors11. However, in that
meta-analysis11, only three studies concerning patients with castration resistant prostate cancer were included.
In the present work, we included patients with both localized PCa and mCRPC in an adequately sufficient data.
Moreover, subgroup analysis was performed, which could provide detailed information for clinical management.
More importantly, we found that NLR has adequate prognostic value for OS and PFS/RFS in mCRPC. Although
chemotherapy and hormone therapy were used, mCRPC commonly occurred after the treatment after few years.
Therefore, the NLR measurement could provide valuable prognostic information for mCRPC and be helpful for
optimal treatment strategies selection. In addition, our results showed increased NLR predicted poor PFS/RFS in
Asians, but not in Caucasians, which could be attributed to the ethnicity heterogeneity. Notably, corticosteroids
were one of the palliative treatment options in patients with mCRPC for 30 years38. Intake of corticosteroids
had immunosuppressive effects, which could influence the value of NLR21. The prognostic value of NLR in PCa
should be evaluated after adjustment on potential confounders including use of corticosteroids. However, only
one21 of the included studies provided the relevant data, thus the analysis could not be conducted in the current
meta-analysis due to insufficient data. Interestingly, Lorente et al.21 found that NLR had independent prognostic
value on OS regardless of corticosteroids usage using multivariable analysis. However, a recent work39 found that,
in patients with melanoma, elevated NLR and corticosteroids before week 1 were associated with poorer OS in
univariate analysis, however, in multivariate analysis, elevated NLR remained an independent prognostic factor
whereas the prognostic efficiency of intake of corticosteroids disappeared. Since corticosteroids were widely used
drugs in mCRPC treatment, further studies should take into account intake of corticosteroids when performing
survival analysis. Furthermore, more large scale studies are needed to explore the effects of use of corticosteroids
on survival.
Although our study was the first meta-analysis concerning NLR in PCa prognostication, there were several
limitations need to be addressed. First, vast majority of included publications employed samples of Caucasian
ethnicity, thus the evaluation of OS and RFS/PFS in Asians might be derived by chance because of sample insuf-
ficiency. Second, Shafique et al.16 recruited all types of PCa patients that could not be classified as any PCa types,

Scientific Reports | 6:22089 | DOI: 10.1038/srep22089 5

www.nature.com/scientificreports/

which may contribute to heterogeneity when subgroup analysis and meta-regression were performed. Third, only
publications in English were included, which could cause language bias for selection. Further investigations are
needed to address the above-mentioned shortcomings.
In summary, our study demonstrated that elevated NLR predict poor OS and PFS/RFS in patients with PCa.
Increased NLR showed consistent prognostic value in mCRPC patients and predict poor PFS/RFS in Asians, but
not in Caucasians. The present findings could provide implications for clinical management of patients with PCa
and further investigations involving large sample size and more ethnic backgrounds are needed.

Methods
Literature search.  A comprehensive literature searching of Pubmed, Embase and Web of Science database
was conducted. The search strategy included the combinations of the following key words: (NLR OR neutro-
phil-lymphocyte ratio OR neutrophil-to-lymphocyte ratio) AND (prostate cancer OR prostate carcinoma OR
prostatic neoplasms OR PCa) AND (prognosis OR survival OR outcome OR recurrence). The last search was
updated on October 17th, 2015. We also manually checked the reference list to identify additional publications.
The published language was limited to English.

Inclusion and exclusion criteria.  Inclusion criteria for publication selection were as follows: (i) the diag-
nosis of PCa for patients was histopathologically confirmed; (ii) the value of NLR was obtained for blood sample
testing; (iii) investigated the association of NLR with PFS, RFS or OS; (iv) provided HRs and 95% CIs for NLR in
OS and (or) PFS/RFS, or HRs and 95%CIs could be calculated according to the raw data provided in the article;
(v) defined the cut-off value of increased NLR; (vi) published in English language.
Major exclusion criteria were as follows: (i) letters, editorials, review articles; (ii) failed to provide data of
interest or insufficient data to estimate HRs and 95%CIs; (iii) failed to identify the cut-off value for elevated NLR;
(iv) animal studies and irrelevant studies.

Data extraction.  Two investigators (XB,G and XS,G) independently gathered information from each eligible
study. The following data was extracted: surname of the first author, study country, year of publication, ethnic
origin of the subjects, sample size, subtype of PCa, treatment method, cut-off value defining elevated NLR and
HRs with corresponding 95% CIs for PFS/RFS and(or) OS. Discrepancies between the two investigators were
settled by discussion.

Statistical analysis.  The HR and the corresponding 95%CI were used to assess the prognostic efficiency of
NLR on PCa. HR and 95% CI were directly extracted from each single study, if provided, or calculated according
to the methods clarified by Tierney40 et al. Cochran’s Q test and Higgins I-squared statistic were applied to test
the heterogeneity of pooled data. I2 >  50% and p <  0.1 indicated significant heterogeneity and random-effects
model was adopted to combine the effective value. I2 <  50% and p >  0.1 were considered as no heterogeneity
and a fixed-effects model was then adopted. Sources of inter-study heterogeneity were explored using subgroup
analysis and meta-regression. Begg’s funnel plot was used to evaluate publication bias. Sensitivity analyses were
carried out to access the robustness of the results. All p values were two-tailed, and statistical significance level
was set at p <  0.05. All statistical analyses were conducted using STATA 12.0 software (STATA Corporation,
College Station, TX).

References
1. Siegel, R. L., Miller, K. D. & Jemal, A. Cancer Statistics, 2015. CA-Cancer J. Clin. 65, 5–29 (2015).
2. Damber, J. E. & Aus, G. Prostate cancer. Lancet. 371, 1710–1721 (2008).
3. Fung, C., Dale, W. & Mohile, S. G. Prostate Cancer in the Elderly Patient. J. Clin. Oncol. 32, 2523–2530 (2014).
4. Gregory, A. D. & Houghton, A. M. Tumor-associated neutrophils: new targets for cancer therapy. Cancer Res. 71, 2411–2416 (2011).
5. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell. 144, 646–674 (2011).
6. Grivennikov, S. I., Greten, F. R. & Karin, M. Immunity, Inflammation, and Cancer. Cell. 140, 883–899 (2010).
7. Hashimoto, K. et al. The impact of preoperative serum C-reactive protein on the prognosis of patients with hepatocellular
carcinoma. Cancer 103, 1856–1864 (2005).
8. Gu, L. et al. The association of platelet count with clinicopathological significance and prognosis in renal cell carcinoma: a systematic
review and meta-analysis. PloS one 10, e0125538, doi: 10.1371/journal.pone.0125538 (2015).
9. Duan, H. et al. Prognostic role of neutrophil-lymphocyte ratio in operable esophageal squamous cell carcinoma. World J
Gastroenterol. 21, 5591–5597 (2015).
10. Cannon, N. A. et al. Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios as Prognostic Factors after Stereotactic Radiation
Therapy for Early-Stage Non-Small-Cell Lung Cancer. J. Thorac. Oncol. 10, 280–285 (2015).
11. Templeton, A. J. et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J
Natl Cancer Inst. 106, dju124, doi: 10.1093/jnci/dju124 (2014).
12. Nuhn, P. et al. Association of pretreatment neutrophil-to-lymphocyte ratio (NLR) and overall survival (OS) in patients with
metastatic castration-resistant prostate cancer (mCRPC) treated with first-line docetaxel. BJU Int. 114, E11–E17 (2014).
13. Templeton, A. J. et al. Simple Prognostic Score for Metastatic Castration-Resistant Prostate Cancer With Incorporation of
Neutrophil-to-Lymphocyte Ratio. Cancer 120, 3346–3352 (2014).
14. Langsenlehner, T. et al. Validation of the neutrophil-to-lymphocyte ratio as a prognostic factor in a cohort of European prostate
cancer patients. World J Urol, 33, 1661–1667 (2015).
15. Linton, A. et al. Glasgow prognostic score as a prognostic factor in metastatic castration-resistant prostate cancer treated with
docetaxel-based chemotherapy. Clin Genitourin Cancer. 11, 423–430 (2013).
16. Shafique, K. et al. Systemic inflammation and survival of patients with prostate cancer: evidence from the Glasgow Inflammation
Outcome Study. Prostate Cancer Prostatic Dis. 15, 195–201 (2012).
17. van Soest, R. J. et al. Neutrophil-to-lymphocyte ratio as a prognostic biomarker for men with metastatic castration-resistant prostate
cancer receiving first-line chemotherapy: data from two randomized phase III trials. Ann Oncol. 26, 743–749 (2015).
18. Yao, A. et al. High neutrophil-to-lymphocyte ratio predicts poor clinical outcome in patients with castration-resistant prostate
cancer treated with docetaxel chemotherapy. Int J Urol. 22, 827–833 (2015).

Scientific Reports | 6:22089 | DOI: 10.1038/srep22089 6

www.nature.com/scientificreports/

19. Sharma, V. et al. The association of preoperative neutrophil to lymphocyte ratio with oncologic outcomes following radical
prostatectomy for prostate cancer. J Urol. 193, e55–e56 (2015).
20. Poyet, C. et al. Pretreatment systemic inflamatory response parameters do not predict the outcome in men with prostate cancer
undergoing radical prostatectomy. J Urol. 193, e817 (2015).
21. Lorente, D. et al. Baseline neutrophil-lymphocyte ratio (NLR) is associated with survival and response to treatment with second-line
chemotherapy for advanced prostate cancer independent of baseline steroid use. Ann Oncol. 26, 750–755 (2015).
22. Lee, H. et al. High preoperative neutrophil-lymphocyte ratio predicts biochemical recurrence in patients with localized prostate
cancer after radical prostatectomy. World J Urol. doi: 10.1007/s00345-015-1701-6 (2015).
23. Kwon, Y. S. et al. Neutrophil and Lymphocyte Counts as Clinical Markers for Stratifying Low-Risk Prostate Cancer. Clin Genitourin
Cancer, doi: 10.1016/j.clgc.2015.07.018 (2015).
24. Bahig, H. et al. Neutrophil count is associated with survival in localized prostate cancer. BMC Cancer 15, 594, doi: 10.1186/s12885-
015-1599-9 (2015).
25. Sumbul, A. T. et al. Neutrophil-to-lymphocyte ratio predicts PSA response, but not outcomes in patients with castration-resistant
prostate cancer treated with docetaxel. Int Urol Nephrol. 46, 1531–1535 (2014).
26. Proctor, M. J. et al. A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer. Br J Cancer 107, 695–699
(2012).
27. Cho, I. R. et al. Pre-treatment neutrophil to lymphocyte ratio as a prognostic marker to predict chemotherapeutic response and
survival outcomes in metastatic advanced gastric cancer. Gastric Cancer. 17, 703–710 (2014).
28. Xiao, W. K. et al. Prognostic significance of neutrophil-lymphocyte ratio in hepatocellular carcinoma: a meta-analysis. BMC Cancer
14, 10, doi: 10.1186/1471-2407-14-117 (2014).
29. Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860–867 (2002).
30. Koizumi, K., Hojo, S., Akashi, T., Yasumoto, K. & Saiki, I. Chemokine receptors in cancer metastasis and cancer cell-derived
chemokines in host immune response. Cancer Sci. 98, 1652–1658 (2007).
31. Roxburgh, C. S. & McMillan, D. C. Role of systemic inflammatory response in predicting survival in patients with primary operable
cancer. Future Oncol. 6, 149–163 (2010).
32. Koh, C. H. et al. Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast
cancer. Br. J. Cancer 113, 150–158 (2015).
33. Li, M. X. et al. Prognostic role of neutrophil- to- lymphocyte ratio in colorectal cancer: A systematic review and meta-analysis. Int J
Cancer. 134, 2403–2413 (2014).
34. Gu, X. B., Tian, T., Tian, X. J. & Zhang, X. J. Prognostic significance of neutrophil-to-lymphocyte ratio in non-small cell lung cancer:
a meta-analysis. Sci Rep. 5, 12493, doi: 10.1038/srep12493 (2015).
35. Szkandera, J. et al. Elevated preoperative neutrophil/lymphocyte ratio is associated with poor prognosis in soft-tissue sarcoma
patients. Br J Cancer. 108, 1677–1683 (2013).
36. Hu, K., Lou, L., Ye, J. & Zhang, S. Prognostic role of the neutrophil-lymphocyte ratio in renal cell carcinoma: a meta-analysis. BMJ
open 5, e006404, doi: 10.1136/bmjopen-2014-006404 (2015).
37. Wei, Y., Jiang, Y. Z. & Qian, W. H. Prognostic role of NLR in urinary cancers: a meta-analysis. PloS one 9, e92079, doi: 10.1371/
journal.pone.0092079 (2014).
38. Ndibe, C., Wang, C. G. & Sonpavde, G. Corticosteroids in the Management of Prostate Cancer: A Critical Review. Curr Treat Options
Oncol. 16, 6, doi: 10.1007/s11864-014-0320-6 (2015).
39. Zaragoza, J. et al. Neutrophil to lymphocyte ratio measured before starting ipilimumab treatment is associated with reduced overall
survival in patients with melanoma. Br J Dermatol, doi: 10.1111/bjd.14155 (2015).
40. Tierney, J. F., Stewart, L. A., Ghersi, D., Burdett, S. & Sydes, M. R. Practical methods for incorporating summary time-to-event data
into meta-analysis. Trials 8, 16, doi: 10.1186/1745-6215-8-16 (2007).

Acknowledgements
This study was supported by Special fund for “Capital clinically characteristic applied research” of Beijing
Municipal Science & Technology Commission (Grant No. Z141107002514160).

Author Contributions
X.B.G., X.S.G., M.W.M. and S.B.Q. defined the research theme. X.B.G., X.S.G., X.Y.L., X.Q. and H.Y. wrote
and revised the main manuscript text; S.Q.S., D.Z. and W.W. prepared all the figures. All authors reviewed the
manuscript.

Additional Information
Competing financial interests: The authors declare no competing financial interests.
How to cite this article: Gu, X. et al. Prognostic significance of neutrophil-to-lymphocyte ratio in prostate
cancer: evidence from 16,266 patients. Sci. Rep. 6, 22089; doi: 10.1038/srep22089 (2016).
This work is licensed under a Creative Commons Attribution 4.0 International License. The images
or other third party material in this article are included in the article’s Creative Commons license,
unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material. To view a copy of this
license, visit http://creativecommons.org/licenses/by/4.0/

Scientific Reports | 6:22089 | DOI: 10.1038/srep22089 7